Prosthetic vessels for stress at vascular graft anastomoses

ABSTRACT

Prosthetic vessels having improved resistance to occlusion by tissue reaction upon implantation by reducing transmural stresses are also disclosed. Prostheses having elliptical cross-sections governed by the maximum strain expected in the natural vessel and possessing a higher bulk compliance than previous designs are provided. Additionally, novel methods are presented for implanting improved prostheses by using angled bias cuts to produce an elliptical cross-section at each end of the natural vessel section receiving the prosthesis. In accordance with preferred embodiments, vessels are provided where the cross-sectional geometry is approximated by the equations: 
     
         a=r.sub.0 [1+2ε (2+ε )].sup.1/2 
    
     and 
     
         b=r.sub.0.

This is a division of application Ser. No. 198,787, filed May 25, 1988,now U.S. Pat. No. 4,938,740, issued on July 3, 1990.

This invention relates to improvements in small vessel prostheses whichreduce both static and dynamic stresses resulting from differences inelastic properties between the prosthesis and the vessel to which it isanastomosed. Such improvements reduce the likelihood of occlusion.Further, this invention is directed to methods for implanting reducedstress prostheses.

BACKGROUND OF THE INVENTION

For a variety of reasons, it is often medically desirable to replace asection of a blood vessel, either a vein or an artery, with a prosthesisrather than using a viable tissue graft. A difficulty frequentlyencountered in the replacement of a natural vessel section with aprosthesis is that, despite successful surgical implantation, theprosthesis occludes and thereby fails in its function. This problem isparticularly troublesome with what can be described as small vesselprostheses, particularly those intended to replace or repair smallarterial sections. The resulting blockage in the artery (lumenocclusion) usually occurs at the sites of the anastomoses and, if theprosthetic material is adequately blood compatible, is primarily due totissue reactions such as endothelial, smooth muscle cell, or fibroblastproliferation, rather than clot formation. There is evidence to suggestthat mismatch at the suture line between the elastic properties of thehost vessel and the prosthesis is a primary contributor to mechanismsunderlying these reactions.

All vessel materials manifest several important viscoelastic properties,the determination of the significance of these properties is dependentupon the application, loading conditions, loading frequencies and othervariables. The nonlinear elastic modulus of most biomaterials dominatestheir mechanical behavior in a vessel application; the variation in thisproperty between natural and prosthetic materials can span orders ofmagnitude. If a vessel is sutured to a prosthesis with an identicalunloaded geometry, the relatively smaller load bearing surface of thesutures tends to impart significant stress concentrations at theinterface, particularly if the prosthesis has a different elasticmodulus. For example, a small artery with a lumen diameter on the orderof 2 mm (0.08 inches), developing a peak strain on the order of 0.1, candevelop peak azimuthal wall stresses on the order of 10⁵ -10⁶ dyne/cm²(1.45-14.5 lb/in²). If a natural vessel is sutured to a prosthesis withan elastic modulus one order of magnitude greater, the resulting stressat a suture can easily achieve a value two orders of magnitude greaterthan the normal peak azimuthal stress. This increased stress burdenbrought about by the mismatch can cause severe tissue reactions whichmay lead to the failure of the implant.

As might be expected, reactions common to viable tissue under stress,e.g., fibroblast and muscle cell proliferation or hypertrophy, collagensynthesis, venous graft "arterialization", etc., can occur in thevessel. For example, research has demonstrated that smooth muscle cellproliferation occurs as a direct consequence of cyclic tensile stress.See, Leung, et al. "A New In Vitro System for Studying Cell Response toMechanical Stimulation", Experimental Cell Research, Vol. 109, pp.285-89, (1977), incorporated herein by reference.

If all other factors remain constant, as lumen diameters increase, wallstress increases in direct proportion to the lumen radius. However,since the cross-sectional area increases in proportion to the square ofthe radius, the occlusive problem is progressively diminished withincreasing lumen diameter, despite similar reactions at the site of theanastomosis. Therefore, although stress reduction is important in allvessel prosthetics, the problem is particularly acute in the range oflumen diameters below about four millimeters. See, Proceedings, Workshopon Blood, Transport Phenomena, and Surfaces, National Institutes ofHealth Publication No. 86-2726 (1986) (hereinafter "NIH Workshop"),incorporated herein by reference.

Previous attempts to solve the problem of stress-induced tissuereactions have largely concentrated on the material surface properties,as well as the mismatch of elastic properties between the vessel and theprosthesis--in other words a search for a "perfect material" to be usedas a prosthesis. Progress has been made by selecting materials andconstructing prostheses for particular site-specific applications. Otherresearch continues. In particular, studies of material properties suchas porosity and compliance, as well as studies of the mechanicalproperties of diseased arteries have been identified as promising areasof reasearch. See, NIH Workshop at 77-78.

Although many areas of research hold promise, there is currently a needwithin the medical profession to have the capability to implant reliableprostheses in patients with diseased or damaged vessels. As reflected bythe current state of the art, there exists at this time no generalsolution to this problem since no material has been found to have therequisite surface and mechanical properties while being biomedicallyacceptable as a prosthesis. There is, therefore, a long-felt butunsolved need for a small diameter prosthetic vessel having improvedelastic properties to eliminate or substantially reduce the stressimparted at the anastomosis.

OBJECTS OF THE INVENTION

It is an object of this invention to provide a class of small vesselprostheses which will reduce the occlusions resulting from reactions tocyclic stresses generated at anastomoses.

It is another object of this invention to provide small vesselprostheses which minimize the stress loading on the natural vesselgenerally without regard to the material utilized.

It is yet another object of this invention to provide a class of smallvessel prostheses which place no excessive stress upon natural vesselsover any expected range of transmural loading experienced followingimplantation.

It is a further object of this invention to provide methods forselecting the geometry of small vessel prostheses such that a bulkcompliance is achieved which results in no untoward stress loading onthe natural vessel.

It is still a further object of this invention to provide methods forgrafting prostheses made in accordance with this invention to smallvessels in a manner that does not develop untoward static or dynamicstresses at the anastomoses.

SUMMARY OF THE INVENTION

In accordance with this invention, a class of small vessel prosthesesare provided which minimize vessel stresses, without primary regard tomaterial property mismatch, by providing an optimal prosthetic geometry.Bulk compliance, as applied to the protheses of this invention, isdefined as an aggregate of material and geometric properties. Everymaterial possesses quantifiable mechanical properties such as itsmodulus of elasticity, modulus of rigidity, Poisson's ratio, etc. fromwhich material behavior under loading can be determined. Further, anygiven geometry has identifiable structural properties defined by itssection modulus, which is derived from the cross-sectional moment ofinertia for a particular geometry. It has been determined that thecompliance attributable to the properties possessed by a particularmaterial within a defined loading range can be relegated to a secondorder consideration if the prosthetic geometry is carefully controlled.Thus, it is now possible to achieve a bulk compliance such that, withessentially no regard to the material chosen, no excessive stressloading is imparted to the natural vessel. The material chosen need onlybe biologically compatible, that is, it must be capable of beinganastomosed to a living vessel without being rejected or otherwisecausing unacceptable thrombus to occur. Prostheses made in accordancewith the present invention can be formed from polyethylene terephthalate(Dacron), polytetraflouroethylene (Teflon) or any other biologicallycompatible material, the material choice now largely a matter of surfaceproperty considerations and physician preference. The method andprostheses of the present invention are useful with any biologicallycompatible material, known or discovered in the future, for use ineither human or veterinary applications.

In accordance with this invention, the interfacial stresses developed insmall vessel prostheses are greatly reduced by sectioning the vessel tobe anastomosed on a prescribed bias such that an elliptic section isdeveloped. The prosthetic vessel is constructed such that in itsunloaded state it possesses substantially the same ellipticcross-section at its anastomotic planes as that selected for the exposedend of the natural vessel. The cross-sectional area of an ellipticvessel increases substantially upon transmural loading while exhibitingrelatively little extensional deformation, which may be defined asalteration in perimeter length between unloaded and loaded states.Therefore, an elliptical geometry is chosen to minimize the stressesimparted upon the natural vessel over the expected range of vesseldeformation.

When the natural and prosthetic vessels are anastomosed, the bias cutscreating the elliptic cross-sections result in a vessel structurepossessing a local directional flow change on the order of 30°-40°.Since the prosthesis' distortions operate primarily in an inextensionaldeformation mode, the natural vessel is not constrained or stressedsignificantly. The result is a significant reduction in tissue stressand as a consequence, tissue reactions, which are believed to be aprimary cause of lumen occlusion.

Accordingly, this invention satisfies the need for a class of smallvessel prostheses which reduces the occurrence of occlusions resultingprimarily from tissue reactions to cyclic stress. The small vesselprostheses of this invention utilize novel geometries which avoidtransferring excessive stresses to the natural vessel over the expectedrange of transmural loading, generally independently of the materialsused. Additionally, this invention is directed to methods for selectingprosthetic geometry such that the bulk compliance achieved significantlyreduces the stress placed upon the natural vessel. Although theprostheses of the present invention possess the same useful propertieswithout regard to size, they represent a particularly useful solution tothe previously described long felt need to prevent occlusion in vesselswith a lumen diameter of less than four millimeters.

This invention also provides methods which minimize the stressesgenerated at the anastomoses when preparing natural vessels to beanastomosed to prostheses made in accordance with this invention.

The features and advantages of the present invention will be more fullyunderstood by reference to the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows an elevation view of a portion of a cylindrical vessel.

FIG. 1B shows an alternative embodiment of the vessel shown in FIG. 1A.

FIG. 2 shows an elevation view of a prosthesis having an approximatelyelliptical cross section at each end.

FIG. 3 depicts a completed graft utilizing a vessel prepared as in FIG.1A and a prosthesis of the invention.

FIG. 4 depicts an alternative embodiment of a completed graft using avessel prepared as in FIG. 1B and a prosthesis of the invention.

FIG. 5 shows a circular cross section of a vessel with radius "r".

FIG. 6 shows the elliptical section formed at the anastomotic plane ofthe natural vessel by bias cuts.

FIG. 7 shows the elliptical cross-section of FIG. 2.

FIG. 8 depicts an embodiment wherein the prosthesis and method of thepresent invention are applied to one end of an extension which isattached to a medical device.

FIG. 1A shows an elevation view of a portion of a cylindrical vessel 10which has been prepared for the grafting of a prosthesis made inaccordance with the present invention by making bias cuts 12 and 14 atan angle α, which is the acute included angle between a cylindrical axis16 and the plane of bias cuts 12 and 14. Shown in FIG. 5, is thecircular cross-section of vessel 10 with lumen 15 and radius "r". FIG. 6illustrates the elliptical section formed at the anastomotic plane ofthe natural vessel by bias cuts 12 and 14, having a major axis 2a and aminor axis 2b.

An alternative embodiment of the present invention is pictured in FIG.1B. As shown, the bias cuts 22 and 24 are made at angle α as in FIG. 1A,however, the cuts are now made generally parallel to each other. Theresulting elliptic shape formed at the anastomotic planes issubstantially the elliptic shape shown in FIG. 6.

FIG. 2 is an elevation view of a prosthesis 20 having an approximatelyelliptical cross-section at each end. It will be appreciated that thecentral portion of the prosthesis may not necessarily be of ellipticcross-section. FIG. 7 illustrates the elliptical cross-section of FIG.2, having major and minor axes approximately equal to those of thevessel 10 at the anastomotic planes, as illustrated in FIG. 6.

FIG. 3 depicts a completed graft utilizing a vessel 10 prepared as shownin FIG. 1A and prosthesis 20 of the present invention. The prosthesis 20has been affixed to the vessel 10 at anastomoses 30 and 40, usingsutures 60 or other means for joining the vessel 10 and prosthesis 20.Also shown are flow vectors 50 and 52 illustrating the flow path changethrough the prosthesis 20. The path change may be described by the angleθ, which is defined as the included acute angle between a first flowvector 50 flowing parallel to the cylindrical axis 16 of the vessel 20,and a second flow vector 52 flowing perpendicular to the plane of thebias cuts 12 and 14. The angle θ can be further described by theequation θ=(90°-α) as can be seen by comparing FIGS. 1 and 3.

FIG. 4 depicts an alternative embodiment of a completed graft utilizinga vessel 10 prepared as shown in FIG. 1B and a prosthesis 20 of thepresent invention. Due to the difference in the relationship between thebias cuts, it can be seen that the prosthesis assumes a somewhatdifferent shape. The embodiment of FIG. 4 possesses the same propertieswhich result in stress reduction at the sites of the anastomoses. Theprosthesis 20 has been affixed to the vessel 10 at anastomoses 30 and40, using sutures 60 or other means for joining the vessel 10 andprosthesis 20. Also shown are flow vectors 50 and 52 illustrating theflow path change through the prosthesis 20. It will be noted thatalthough the actual flow path differs from that shown in FIG. 3, thepath change may still be described by the angle θ which is defined inthe same manner as described above.

FIG. 8 depicts an embodiment wherein the prosthesis and method of thepresent invention are applied to one end of an extension 60 which isattached to a medical device 70. This device can be an infusionapparatus, a drug pump, an artificial organ or any other apparatusattached to any natural vessel. One of ordinary skill in the art willappreciate that the distal end 62 of the extension should beapproximately elliptical in cross-section in accordance with the presentinvention. The portion of the extension 60 which lies between the distalend 62 and the medical device 70 need not be an ellipticalcross-section, in the same manner as the central portion of theprosthesis shown in FIG. 2.

One of ordinary skill in the art will be able to construct prostheses inaccordance with the present invention in view of the following exemplaryprocedure, giving due consideration to the constraints discussed.

When constructing small vessel prostheses having novel configurationswhich, in accordance with the present invention, reduce stress at theanastomoses, the following constraints generally govern the geometry ofsuch designs:

1. In the unloaded state or under minimal transmural loading, thecircular vessel should not appreciably distort the prosthesis. Thisconstraint generally requires that, given an approximately circularvessel, the unloaded lumen radius r₀ should approximate the minorsemi-axis of the elliptic section of the prosthesis.

2. In the fully stressed state an initially elliptic prosthesis shouldnot constrain or place significant stresses upon the natural vessel.This constraint requires that prosthetic distortion at the anastomosesoperate primarily in the inextensional deformation mode, that is, thealteration in perimeter length between unloaded and loaded states shouldbe minimized.

In accordance with a preferred embodiment of the present invention, anelliptical cross-section is chosen because of its high degree ofgeometric compliance. Although other geometries also exhibit thisdesirable property, since vessels generally exhibit roughly circularcross-sections, an analysis of the geometric and physicalcharacteristics of such an interface may be undertaken without unduecomplexity.

If an elliptical or near elliptical shape is assumed for the prosthesis,the cross-section may be described by defining major and minor axes, 2aand 2b. In order to minimize strain upon the unloaded vessel, the minorsemi-axis, "b", should be approximately equal to the unloaded vesselradius, r₀. In order to completely define the geometry of theprosthesis, the length of the major axis 2a should also be determined.When a major axis length is determined, the first constraint isessentially complied with by selecting an appropriate bias angle for thenatural vessel, such that the anastomotic plane is approximately equalto the prosthetic geometry. In other words, with respect to the firstconstraint, the natural vessel should be cut at an angle such that theexposed end of the natural vessel has an elliptical shape approximatelythe same as the unloaded shape of the prosthesis being used.

It is well known that vessels carrying blood or other body fluids tendto undergo expansion upon loading. The pressure of the fluid causes arelatively uniform expansion of the perimeter of the vessel which may beexpressed as a strain, that is, the difference between the expanded andunexpanded vessel perimeter length divided by the unexpanded perimeterlength. This measure of strain is unitless or is sometimes expressed asinches/inch (mm/mm). When fully loaded, a relatively circular naturalvessel expands slightly to a diameter r₁ and circumference l₁. If theincremental increase in radius is Δr, the radial expansion can bedescribed as:

    r.sub.1 =(r.sub.0 +Δr)

and:

    l.sub.1 =2πr.sub.1

By minimizing the alteration in perimeter length of the prosthesis atthe anastomotic plane between loaded and unloaded states, the secondconstraint governing the design of prostheses made in accordance withthis invention may generally be complied with. This can be accomplishedby setting the circumference of the prosthesis, l_(p), to beapproximately equal to l₁. Thus, when the vessel distends, theprosthesis places only minimal restraint upon it. Therefore, it is seenthat: ##EQU1##

Substituting r₀ for "b", (r₀ +Δr) for r₁, and solving for a² yields:

    a.sup.2 =r.sub.0.sup.2 +4r.sub.0 Δr+2Δr.sup.2  (1)

Strain, ε, may be defined as change in length divided by total length:##EQU2## And therefore:

    Δr=r.sub.0 ε

Substituting r₀ ε for Δ_(r) in equation (1) above and solving for "a"results in an expression for the relationship between ellipse geometryand vessel strain:

    a=r.sub.0 [1+2ε(2+ε)].sup.1/2              (2)

This expression shows that the initial eccentricity is independent ofabsolute vessel size but dependent upon expected maximum vesselazimuthal strain. The strain expected in a particular vessel is usuallyknown within the art; for example, in small diameter blood vessels, theexpected strain is on the order of 0.1, with an expected maximum of 0.2.The strain expected within a particular type of vessel may be easilydetermined experimentally if a value is not already known.

The preceding considerations allow the geometry of an elliptical vesselpossessing the characteristics of minimizing the stresses imparted onthe natural vessel to be defined in accordance with this invention. Fora given vessel with radius r₀ and a given strain ε, the major semi-axis,"a", of the elliptical prosthesis may now be calculated, and the minorsemi-axis "b" can be set approximately equal to r₀.

An elliptical prosthesis designed to conform to the above constraints ispreferably grafted to a natural vessel in a manner which takes fulladvantage of the increased compliance resulting from its novel geometry.Therefore, a method of grafting a prosthesis made in accordance with thepresent invention is provided. This method has the further advantage ofproviding a greater perimeter length over which sutures or other meansof forming the anastomosis may be spaced, thus further reducing stressat each suture.

In order to implant a prosthesis made in accordance with the presentinvention, it is necessary to cut the natural vessel on a bias toproduce an elliptical cross-section approximately the same shape as theelliptical cross-section of the prosthesis when the natural vessel isviewed perpendicular to the plane of the bias cut. If α is defined asthe acute included angle between the cylindrical axis of the vessel andthe anastomotic plane of the natural vessel, and "a" is the majorsemi-axis of the elliptical cross-section of the prosthesis, and sincer₀ is the radial distance between the cylindrical axis and the perimeterof the lumen, the geometry may be described by the following equation:##EQU3## Solving for α: ##EQU4##

From this equation it is seen that the angle of the bias is notdependent upon the relative vessel size, but upon the expected strainvalue. For example, an expected strain value ε≈0.1 dictates that thebias cut angle α is about 57°.

Since the natural vessel is cut on a bias and joined to a prosthesiswhose ends are generally perpendicular to its immediate central axis,the resulting implant section induces a change in the flow path of thecontained fluid. For the above example, the change in direction of flowis about 33°. A change in flow direction may introduce flow relatedfactors that may affect regional transport, clotting, local endothelialcell thickening, etc. In general these problems are expected to berelatively insignificant in comparison to the stress-induced problemswhich are though to be the primary cause of occlusion in other smallvessel prostheses.

A prothesis made in accordance with this invention is implanted aftermaking the prescribed bias cuts in the natural vessel by suturing eachend of the elliptical prosthesis to the prepared elliptical faces of thenatural vessel. The present invention contemplates other methods offorming the anastomoses, and is not limited to sutures. Thus, adhesives,staples, and other means for fastening are included within the scope ofthis invention. The prosthesis takes a generally arc-shaped path betweenthe two bias cuts, inducing the change in direction of flow discussed,but as one skilled in the art will appreciate, the completed prosthesisplaces no excessive stress upon the natural vessel/prosthesis interface,even upon full loading. Alternatively, the bias cuts may be made in amanner such that they are generally parallel; thus the prosthesis willtake on a slightly "S"-shaped configuration. This configuration alsoprovides stress reduction at the anastomotic planes.

The application of the article and method of the present invention isnot limited to the replacement of small arterial sections. Using theconcepts discussed above, one of ordinary skill in the art will be ableto construct extensions or interfaces to medical devices, which may haveone or more inputs and outputs, so as to take advantage of thestress-reduction benefits of the present invention. The term medicaldevice is meant to encompass any object which is surgically attached toa patient or animal by anastomoses. Such devices may include but are notlimited to medichemiant infusion devices, blood pumping apparatus,artificial hearts, artificial endocrine organs, filtration devices,dialysis devices or any connection to any medical apparatus which isanastomosed to a patient or animal subject.

While certain embodiments have been set forth with particularity,persons of ordinary skill in the art will recognize that otherembodiments may be possible employing the spirit of this invention.

What is claimed is:
 1. An implantable prosthetic vessel for attachmentto a generally elliptical opening of a natural vessel, the prostheticvessel having improved resistance to occlusion upon implantation,comprising:an elongated tubular portion, formed from a biologicallycompatible material, having at least one end having a generallyelliptical cross-section at an anastomotic plane perpendicular to acentral axis of said tubular portion, the elliptical cross-sectionhaving approximately the same dimensions as the elliptical opening towhich the prosthetic vessel is attached thereby reducing both static anddynamic stresses between the prosthetic vessel and the natural vessel.2. The prosthetic vessel of claim 1, wherein said biologicallycompatible material is polytetrafluoroethylene.
 3. The prosthetic vesselof claim 1, wherein said biologically compatible material ispolyethylene terephthalate.
 4. The prosthetic vessel of claim 1, whereinthe distance across the lesser of the geometric axes of said ellipticalcross-section is less than about 4 mm (0.16 inches).
 5. The prostheticvessel of claim 1, wherein said generally elliptical cross-section isapproximately defined by the equations:

    a=r.sub.0 [1+2ε(2+ε)].sup.1/2

and

    b=r.sub.0

Where "a" is the major semi-axis of said generally ellipticcross-section, "b" is the minor semi-axis of said generally ellipticcross-section, "r₀ " is the unloaded inner diameter of the naturalvessel, and "ε" is a selected value for the strain expected within thenatural vessel.
 6. A generally tubular extension made in accordance withclaim 1 and being attached to a medical device, an opposite end of saidtubular extension having a generally elliptical cross-section in a planeperpendicular to said central axis.